Contrasting population genetic patterns within the white-throated sparrow genome (Zonotrichia albicollis)

<p>Abstract</p> <p>Background</p> <p>The level of nucleotide diversity observed across the genome is positively correlated with the local rate of recombination. Avian karyotypes are typified by large variation in chromosome size and the rate of recombination in birds has been shown to be negatively correlated with chromosome size. It has thus been predicted that nucleotide diversity is negatively correlated with chromosome size in aves. However, there is limited empirical evidence to support this prediction.</p> <p>Results</p> <p>Here we sequenced 27 autosomal and 12 sex chromosome-linked loci in the white-throated sparrow (<it>Zonotrichia albicollis</it>) to quantify and compare patterns of recombination, linkage disequilibrium (LD), and genetic diversity across the genome of this North American songbird. Genetic diversity on the autosomes varied up to 8-fold, with the lowest diversity observed on the macrochromosomes and the highest diversity on the microchromosomes. Genetic diversity on the sex chromosomes was reduced compared to the autosomes, the most extreme difference being a ~300-fold difference between the W chromosome and the microchromosomes. LD and population structure associated with a common inversion polymorphism (ZAL2/2^m) in this species were found to be atypical compared to other macrochromosomes, and nucleotide diversity within this inversion on the two chromosome arrangements was more similar to that observed on the Z chromosome.</p> <p>Conclusions</p> <p>A negative correlation between nucleotide diversity and autosome size was observed in the white-throated sparrow genome, as well as low levels of diversity on the sex chromosomes comparable to those reported in other birds. The population structure and extended LD associated with the ZAL2/2^mchromosomal polymorphism are exceptional compared to the rest of the white-throated sparrow genome.</p

A media advocacy intervention linking health disparities and food insecurity

Media advocacy is a well-established strategy for transmitting health messages to the public. This paper discusses a media advocacy intervention that raised issues about how the public interprets messages about the negative effects of poverty on population health. In conjunction with the publication of a manuscript illustrating how income-related food insecurity leads to disparities related to the consumption of a popular food product across Canada (namely, Kraft Dinner®), we launched a media intervention intended to appeal to radio, television, print and Internet journalists. All the media coverage conveyed our intended message that food insecurity is a serious population health problem, confirming that message framing, personal narratives and visual imagery are important in persuading media outlets to carry stories about poverty as a determinant of population health. Among politicians and members of the public (through on-line discussions), the coverage provoked on-message as well as off-message reactions. Population health researchers and health promotion practitioners should anticipate mixed reactions to media advocacy interventions, particularly in light of new Internet technologies. Opposition to media stories regarding the socio-economic determinants of population health can provide new insights into how we might overcome challenges in translating evidence into preventive interventions

Increased Collagen-Linked Pentosidine Levels and Advanced Glycosylation End Products in Early Diabetic Nephropathy

RATIONALE: Advanced glycosylation end products (AGEs) may play an important role in the development of diabetic vascular sequelae. An AGE cross-link, pentosidine, is a sensitive and specific marker for tissue levels of AGEs. OBJECTIVES: To evaluate the role of AGEs in the development of diabetic nephropathy and retinopathy, we studied pentosidine levels and the clinical characteristics of 48 subjects with insulin-dependent diabetes mellitus. Diabetic nephropathy was classified as normal, microalbuminuria, or gross proteinuria, and retinopathy was graded as none, background, or proliferative. NEWLY OBSERVED FINDINGS: Significant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03 +/- 9.47 vs 76.46 +/- 6.37 pmol/mg col) when compared with normal (56.96 +/- 3.26 pmol/mg col). Multivariate analysis to correct for age, duration of diabetes, and gender did not modify the results. Elevated pentosidine levels were also found in those with proliferative when compared with those with background retinopathy (75.86 +/- 5.66 vs 60.42 +/- 5.98 pmol/mg col) (P \u3c 0.05). CONCLUSIONS: Microalbuminuria is associated with elevated levels of pentosidine similar to those found in overt diabetic nephropathy suggesting that elevated AGE levels are already present during the earliest detectable phase of diabetic nephropathy

The Role of Tobacco, Alcohol, and Obesity in Neoplastic Progression to Esophageal Adenocarcinoma: A Prospective Study of Barrett's Esophagus

Background: Esophageal adenocarcinoma (EA) incidence in many developed countries has increased dramatically over four decades, while survival remains poor. Persons with Barrett's esophagus (BE), who experience substantially elevated EA risk, are typically followed in surveillance involving periodic endoscopy with biopsies, although few progress to EA. No medical, surgical or lifestyle interventions have been proven to safely lower EA risk. Design: We investigated whether smoking, obesity or alcohol could predict progression to EA in a prospective cohort of 411 BE patients. Data were collected during personal interview. Adjusted hazard ratios (HR) were estimated using Cox regression. Results: 39% had body mass index (BMI) over 30 and 64% had smoked cigarettes. Main analyses focused on those with at least 5 months of follow-up (33,635 person-months), in whom 45 developed EA. Risk increased by 3% per year of age (trend p-value 0.02), with approximate doubling of risk among males. EA risk increased with smoking pack-years (trend p-value 0.04) and duration (p-value 0.05). Compared to never-smokers, the HR for those in the highest pack-year tertile was 2.29 (95%CI 1.04–5.07). No association was found with alcohol or BMI, whereas a suggestion of increased risk was observed in those with higher waist-hip ratio, especially among males. Conclusion: EA risk significantly increased with increasing age and cigarette exposure. Abdominal obesity, but not BMI, was associated with a modest increased risk. Continued follow-up of this and other cohorts is needed to precisely define these relationships so as to inform risk stratification and preventive interventions

What Should a Psychiatrist Know About Genetics? Review and Recommendations From the Residency Education Committee of the International Society of Psychiatric Genetics.

The International Society of Psychiatric Genetics (ISPG) created a Residency Education Committee with the purpose of identifying key genetic knowledge that should be taught in psychiatric training programs. Thirteen committee members were appointed by the ISPG Board of Directors, based on varied training, expertise, gender, and national origin. The Committee has met quarterly for the past 2 years, with periodic reports to the Board and to the members of the Society. The information summarized includes the existing literature in the field of psychiatric genetics and the output of ongoing large genomics consortia. An outline of clinically relevant areas of genetic knowledge was developed, circulated, and approved. This document was expanded and annotated with appropriate references, and the manuscript was developed. Specific information regarding the contribution of common and rare genetic variants to major psychiatric disorders and treatment response is now available. Current challenges include the following: (1) Genetic testing is recommended in the evaluation of autism and intellectual disability, but its use is limited in current clinical practice. (2) Commercial pharmacogenomic testing is widely available, but its utility has not yet been clearly established. (3) Other methods, such as whole exome and whole genome sequencing, will soon be clinically applicable. The need for informed genetic counseling in psychiatry is greater than ever before, knowledge in the field is rapidly growing, and genetic education should become an integral part of psychiatric training

Cluster randomized controlled trial of an aged care specific leadership and management program to improve work environment, staff turnover, and care quality

OBJECTIVE To evaluate the effectiveness of a leadership and management program in aged care. DESIGN Double-blind cluster randomized controlled trial. SETTING Twelve residential and community-aged care sites in Australia. PARTICIPANTS All care staff employed for 6 months or longer at the aged care sites were invited to participate in the surveys at 3 time points: baseline (time 1), 9 months from baseline (time 2), and 9 months after completion of time 2 (time 3) from 2011 to 2013. At each time point, at least 500 care staff completed a survey. At baseline (N = 503) the largest age group was 45 to 54 years (37%), and the majority of care staff were born in Australia (70%), spoke English (94%), and had at least completed secondary education (57%). INTERVENTION A 12-month Clinical Leadership in Aged Care (CLiAC) program for middle managers, which aimed to further develop their leadership and management skills in creating positive workplace relationships and in enabling person-centered, evidence-based care. MAIN OUTCOME MEASURES The primary outcomes were care staff ratings of the work environment, care quality and safety, and staff turnover rates. Secondary outcomes were care staff's intention to leave their employer and profession, workplace stress, job satisfaction, and cost-effectiveness of implementing the program. Absenteeism was excluded due to difficulty in obtaining reliable data. Managers' self-rated knowledge and skills in leadership and management are not included in this article, which focuses on care staff perceptions only. RESULTS At 6 months after its completion, the CLiAC program was effective in improving care staff's perception of management support [mean difference 0.61, 95% confidence interval (CI) 0.04-1.18; P = .04]. Compared with the control sites, care staff at the intervention sites perceived their managers' leadership styles as more transformational (mean difference 0.30, 95% CI 0.09-0.51; P = .005), transactional (mean difference 0.22, 95% CI 0.05-0.39; P = .01), and less passive avoidant (mean difference 0.30, 95% CI 0.07-0.52; P = .01); and were rated higher on the overall leadership outcomes (mean difference 0.35, 95% CI 0.13-0.56; P = .001) as well as individual manager outcomes: extra effort (P = .004), effectiveness (P = .001), and satisfaction (P = .01). There was no evidence that CLiAC was effective in reducing staff turnover, or improving patient care quality and safety. CONCLUSIONS While the CLiAC leadership program had direct impact on the primary process outcomes (management support, leadership actions, behaviors, and effects), this was insufficient to change the systems required to support care service quality and client safety. Nevertheless, the findings send a strong message that leadership and management skills in aged care managers can be nurtured and used to change leadership behaviors at a reasonable cost

Sorption of metals by extracellular polymers from the cyanobacterium Microcystis aeruginosa fo. flos-aquae strain C3-40

The sorption of cadmium (II), copper (II), lead (II),manganese (II), and zinc (II) by purified capsularpolysaccharide from the cyanobacterium Microcystis aeruginosafo. flos-aquae strainC3-40 was examined by four methods: equilibriumdialysis, metal removal from solution as detected byvoltammetry, metal accumulation by capsule-containingalginate beads, and calorimetry. The polysaccharide's saturation binding capacities for these metals rangedfrom 1.2 to 4 mmol of metal g-1 of capsule, whichcorresponds to 1 metal equivalent per 2 to 4saccharide subunits of the polymer. Competitionbetween paired metals was tested with simultaneous andsequential additions of metal. Cadmium (II) andlead (II), as well as lead (II) and zinc (II), competedrelatively equally and reciprocally for polymerbinding sites. In contrast, manganese (II) stronglyinhibited the binding of cadmium (II) and lead (II), butitself was not substantially inhibited by either theprior or simultaneous adsorption of cadmium (II) or lead (II).The data are interpreted with respect to overlap ofbinding sites and possibilities of altered polymerconformation or solvation. Calorimetric studies oflead (II) and cadmium (II) association reactions withthe polysaccharide suggest that the enthalpies aresmall and that the reactions may be driven by entropy

Ethanol Impairs Estrogen Receptor Signaling Resulting in Accelerated Activation of Senescence Pathways, Whereas Estradiol Attenuates the Effects of Ethanol in Osteoblasts

Epidemiological and animal studies have suggested that chronic alcohol consumption is a major risk factor for osteoporosis. Using bone from cycling female rats infused chronically with ethanol (EtOH) in vivo and osteoblastic cells in vitro, we found that EtOH significantly increased estrogen receptor α (ERα) and β (ERβ) mRNA and ERα protein levels. Treatment with 17β-estradiol (E2) in vivo and in vitro interfered with these effects of EtOH on bone and osteoblastic cells. ERα agonist propylpyrazoletriol (PPT) and ERβ agonist diarylpropionitrile (DPN) attenuated EtOH-induced ERα and ERβ gene overexpression, respectively. Similar to the ER antagonist ICI 182780, EtOH blocked nuclear translocation of ERα-ECFP in the presence of E2 in UMR-106 osteoblastic cells. EtOH also downregulated ERE-luc reporter activity. On the other hand, EtOH by itself upregulated some common ERα- and ERβ-mediated genes apparently by an ER-independent pathway. EtOH also transactivated the luciferase activity of the p21 promoter region independent of additional exogenous ERα, activated p21 and p53, and stimulated senescence-associated β-galactosidase activity in rat stromal osteoblasts. E2 treatment attenuated these EtOH actions. We conclude that inhibitory cross-talk between EtOH and E2 in osteoblasts on ERs, p53/p21, and cell senescence provides a pathophysiologic mechanism underlying bone loss and the protective effects of estrogens in alcohol-exposed females

On-chip label-free protein analysis with downstream electrodes for direct removal of electrolysis products.

The ability to apply highly controlled electric fields within microfluidic devices is valuable as a basis for preparative and analytical processes. A challenge encountered in the context of such approaches in conductive media, including aqueous buffers, is the generation of electrolysis products at the electrode/liquid interface which can lead to contamination, perturb fluid flows and generally interfere with the measurement process. Here, we address this challenge by designing a single layer microfluidic device architecture where the electric potential is applied outside and downstream of the microfluidic device while the field is propagated back to the chip via the use of a co-flowing highly conductive electrolyte solution that forms a stable interface at the separation region of the device. The co-flowing electrolyte ensures that all the generated electrolysis products, including Joule heat and gaseous products, are flowed away from the chip without coming into contact with the analytes while the single layer fabrication process where all the structures are defined lithographically allows producing the devices in a simple yet highly reproducible manner. We demonstrate that by allowing stable and effective application of electric fields in excess of 100 V cm-1, the described platform provides the basis for rapid separation of heterogeneous mixtures of proteins and protein complexes directly in their native buffers as well as for the simultaneous quantification of their charge states. We illustrate this by probing the interactions in a mixture of an amyloid forming protein, amyloid-β, and a molecular chaperone, Brichos, known to inhibit the process of amyloid formation. The availability of a platform for applying stable electric fields and its compatibility with single-layer soft-lithography processes opens up the possibility of separating and analysing a wide range of molecules on chip, including those with similar electrophoretic mobilities